Smad7 drives cisplatin resistance in ovarian cancer via a PRMT5-dependent mechanism

Jinlong Ji1, Kexin Wang1, Geshuyi Chen1

  • 1Department of Gynaecology, Affiliated Hospital 2 of Nantong University and Nantong First People's Hospital, Nantong City, Jiangsu Province 226000, China.

Tissue & Cell
|January 13, 2026
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) drives cisplatin resistance in ovarian cancer by methylating Smad7, activating STAT3 signaling. Targeting this PRMT5-Smad7 axis offers a potential strategy to overcome treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Acquired cisplatin resistance is a significant obstacle in treating ovarian cancer.
  • Understanding the molecular mechanisms underlying this resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of protein arginine methyltransferase 5 (PRMT5) in acquired cisplatin resistance in ovarian cancer.
  • To elucidate the molecular mechanism by which PRMT5 contributes to cisplatin resistance.

Main Methods:

  • Utilized cisplatin-resistant ovarian cancer cell lines (A2780/DDP, SKOV3/DDP).
  • Performed PRMT5 and Smad7 knockdown experiments.
  • Conducted co-immunoprecipitation assays and in vitro methylation studies.
  • Analyzed STAT3 signaling pathway activation.
  • Employed a xenograft mouse model for in vivo validation.

Main Results:

  • PRMT5 knockdown inhibited proliferation, colony formation, migration, and invasion, while promoting apoptosis in resistant cells.
  • PRMT5, complexed with MEP50, methylates Smad7 at R57, activating STAT3 signaling.
  • In vivo Smad7 knockdown suppressed tumor growth and altered expression of proliferation, invasion, and metastasis markers.

Conclusions:

  • Smad7 is a critical driver of cisplatin resistance in ovarian cancer.
  • The PRMT5-Smad7 interaction and subsequent Smad7 methylation by PRMT5 promote oncogenic signaling.
  • The PRMT5-Smad7 axis represents a potential therapeutic target for overcoming cisplatin resistance in ovarian cancer.

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